Nitric oxide synthase in experimental autoimmune myocarditis dysfunction

This study reports the expression of inducible nitric oxide synthase (NOS) in heart from autoimmune myocarditis mice associated with an alteration in their contractile behavior By mean of the production of [U-C-14]citrulline from [U-C-14]arginine and immunoblot assay, the expression of iNOS was demo nstrated in autoimmune atria that was normally absent. The iNOS activity de creased with administration of dexametasone and in mice treated with monocl onal anti-interferon-gamma antibody (anti-IFN-gamma mAb). The inhibitors of protein kinase C activity (staurosporine) but not calcium/ calmodulin (tri fluoperazine) attenuated the iNOS activity Moreover, autoimmune atria prese nted contractile alterations (lower values of dF/dt than control). The in v ivo treatment:with inhibitors of NOS activity or anti-IFN-gamma mAb or dexa metasone improved the contractile activity of autoimmune atria with no chan ge in the contractility of normal atria. The results suggest that the infil trative cells in myocarditis heart have a potential role in cardiac dysfunc tion by production of IFN-gamma and subsequent expression of iNOS, that in turn alter the contractile behavior of the heart. The data indicate that cy tokines induced activation of L-arginine nitric oxide pathway in myocarditi s atria leading to contractile dysfunction. (C) 1998 Academic Press.